High-fat-induced intestinal permeability dysfunction associated with altered fecal bile acids

AIM:To investigate whether high-fat-feeding is associated with increased intestinal permeability via alterations in bile acid metabolism.METHODS:Male C57Bl/6J mice were fed on a high-fat (n=26) or low-fat diet (n=24) for 15 wk.Intestinal permeability was measured from duodenum,jejunum,ileum and colon in an Ussing chamber system using 4 kDa FITC-labeled dextran as an indicator.Fecal bile acids were analyzed with gas chromatography.Segments of jejunum and colon were analyzed for the expression of farnesoid X receptor (FXR) and tumor necrosis factor (TNF).RESULTS:Intestinal permeability was significantly increased by high-fat feeding in jejunum (median 0.334 for control vs 0.393 for high-fat,P=0.03) and colon (0.335 for control vs 0.433 for high-fat,P=0.01),but not in duodenum or ileum.The concentration of nearly all identified bile acids was significantly increased by high-fat feeding (P<0.001).The proportion of ursodeoxycholic acid (UDCA) in all bile acids was decreased (1.4%±0.1% in high-fat vs 2.8%±0.3% in controls,P<0.01) and correlated inversely with intestinal permeability (r=-0.72,P=0.01).High-fat feeding also increased jejunal FXR expression,as well as TNF expression along the intestine,especially in the colon.CONCLUSION:High-fat-feeding increased intestinal permeability,perhaps by a mechanism related to bile acid metabolism,namely a decreased proportion of fecal UDCA and increased FXR expression.

AIM： To investigate whether high-fat-feeding is associ- ated with increased intestinal permeability via altera- tions in bile acid metabolism. METHODS： Male C57BI/6J mice were fed on a high-fat （n = 26） or low-fat diet （n = 24） for 15 wk. Intestinal permeability was measured from duodenum, jejunum, ileum and colon in an Ussing chamber system using 4 kDa FITC-labeled dextran as an indicator. Fecal bile ac- ids were analyzed with gas chromatography. Segments of jejunum and colon were analyzed for the expression of farnesoid X receptor （FXR） and tumor necrosis factor